Enterococcus faecalis persists and replicates intracellularly within neutrophils

SUMMARY

Chronic wound infection is a major global public health issue, with Enterococcus faecalis among the most commonly isolated pathogens from such wounds. Neutrophils are short-lived immune cells critical for host defence, yet E. faecalis-neutrophil interactions are poorly understood. Here, the authors show that instead of eliminating E. faecalis, neutrophils provide a niche for intracellular persistence and replication, potentially prolonging infection and inflammation at the wound site. In murine wound beds and ex vivo wound cells, intracellular E. faecalis was detected in recruited neutrophils at 24 h post-infection (h p.i). Unexpectedly, extended infection did not induce neutrophil death. Rather, E. faecalis infection significantly prolonged the life spans of both murine and human neutrophils in vitro compared to uninfected controls. Quantification of intracellular CFU revealed that E. faecalis were phagocytosed regardless of opsonization and persisted intracellularly up to 24 h p.i. This finding was confirmed via transmission electron microscopy and confocal microscopy. Blinded quantification and fluorescent D-amino acid staining, which marks newly synthesised bacterial peptidoglycan, revealed active replication within murine neutrophils between 6 and 18 h p.i., followed by a predominantly persistent phase between 18 and 24 h p.i. Infected murine neutrophils remained immunologically active, secreting pro-inflammatory and chemoattractant cytokines. These findings highlight an underappreciated intracellular lifestyle for E. faecalis that may contribute to its ability to persist in chronic wounds and contribute to biofilm-associated infections.

Read the full article: https://doi.org/10.1128/iai.00364-25

WHY IS THIS IMPORTANT?

Chronic wounds are a major health problem worldwide, often slow to heal and prone to infection. This study shows that Enterococcus faecalis, a common wound bacterium, can survive and even multiply inside neutrophils, the immune cells that usually kill bacteria. Instead of dying, infected neutrophils live longer and continue sending inflammatory signals, which can prolong infection and tissue damage. Understanding this hidden “Trojan horse” behaviour of E. faecalis may explain why some infections persist despite a strong immune response and antibiotic treatment. These findings could help develop new therapies to clear stubborn infections and improve healing in patients with chronic wounds.

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